‡Aspirin is a brand name in Canada; acetylsalicylic acid is the generic name. ASA, a commonly used designation for aspirin (or acetylsalicylic acid) in both the U.S. and Canada, is the term used in Canadian product labeling.Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

For more information on the managment of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).Treatment of overdose

For aspirin:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage.

Administering activated charcoal.

Specific treatment—Administering blood or Vitamin K1 if necessary to treat hemorrhaging. See the package insert or Vitamin K (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Monitoring serum salicylate concentration until it is apparent that the concentration is decreasing to the nontoxic range. Salicylate concentrations of 50 mg per 100 mL 2 hours after ingestion indicate serious toxicity; salicylate concentrations above 80 mg per 100 mL 2 hours after ingestion indicate possible fatality. In addition, prolonged monitoring may be necessary in massive overdosage because absorption may be delayed; if a determination performed prior to 6 hours after ingestion fails to show a toxic salicylate concentration, the determination should be repeated. Salicylate concentrations of 45 to 65 mg per 100 mL 6 hours after ingestion or 35 to 55 mg per 100 mL 12 hours after ingestion indicate a mild degree of toxicity; salicylate concentrations of 65 to 90 mg per 100 mL 6 hours after ingestion or 55 to 75 mg per 100 mL 12 hours after ingestion indicate a moderate degree of toxicity; and salicylate concentrations of 90 mg (or more) per 100 mL 6 hours after ingestion or 75 mg (or more) per 100 mL 12 hours after ingestion indicate a severe degree of toxicity.

Monitoring for pulmonary edema and instituting appropriate therapy if required.

To enhance elimination—Inducing forced alkaline diuresis to increase salicylate excretion. However, bicarbonate should not be administered orally for this purpose because salicylate absorption may be increased. Also, if acetazolamide is used, the increased risk of severe metabolic acidosis and salicylate toxicity (caused by increased penetration of salicylate into the brain because of metabolic acidosis) must be considered. Some emergency care practitioners recommend that acetazolamide not be used at all in the treatment of salicylate overdose. Others state that acetazolamide may be used, provided that precautions are taken to prevent systemic metabolic acidosis, such as concurrent administration of an alkaline intravenous solution, e.g., one that contains sodium bicarbonate or sodium lactate.

Supportive care—Correcting hyperthermia; fluid, electrolyte, and acid-base imbalances; ketosis; and plasma glucose concentration as needed. Monitoring and supporting vital functions. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.

For opioid analgesics:
To decrease absorption—Emptying the stomach by induction of emesis or gastric lavage. However, treatment of respiratory depression or other potentially life-threatening adverse effects must take precedence.

Specific treatment—Administering the opioid antagonist naloxone. Larger doses of naloxone may be required to reverse the effects of pentazocine or propoxyphene than are required to antagonize the effects of other opioids. See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Continuing to monitor the patient (mandatory because the duration of action of the opioid analgesic may exceed that of naloxone) so that additional antagonist may be administered as needed. Alternatively, initial treatment may be followed by continuous intravenous infusion of naloxone, with the rate of infusion being adjusted according to patient response. The fact that naloxone may also antagonize the analgesic actions of opioid analgesics and may precipitate withdrawal symptoms in physically dependent patients must be kept in mind.

Supportive care—Establishing adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled respiration.

Administering intravenous fluids, vasopressors, and other supportive measures as needed. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Narcotic Analgesics and Aspirin (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):Before using this medication» Conditions affecting use, especially:Sensitivity to the opioid considered for use, to aspirin, or to nonsteroidal anti-inflammatory drugs (NSAIDs), history of

Pregnancy—Aspirin and opioid analgesics cross the placenta; high-dose chronic use or abuse of aspirin in the third trimester may be hazardous to the mother as well as the fetus and/or neonate, causing heart problems in fetus or neonate and/or bleeding in mother, fetus, or neonate; high-dose chronic use or abuse may also prolong and complicate labor and delivery; also, regular use of opioids by pregnant women may cause physical dependence in the fetus and withdrawal symptoms in the neonate; not taking aspirin during the third trimester unless prescribed by physician

Breast-feeding—Aspirin, codeine, and propoxyphene are distributed into breast milk

Use in children and in teenagers——Checking with physician before giving to children or teenagers with symptoms of acute febrile illness, especially influenza or varicella, because of the risk of Reye's syndrome; also, increased susceptibility to aspirin toxicity in children, especially with fever and dehydration; also, children up to 2 years of age are more susceptible to the effects of opioids, especially respiratory depression; in addition, children may be more likely to experience opioid-induced paradoxical CNS excitation during therapy

Use in the elderly—Increased risk of aspirin toxicity and of opioid-induced adverse effects, especially respiratory depressionOther medications, especially alcohol or other CNS depressants, anticoagulants, antidiabetic agents (oral), those cephalosporins that may cause hypoprothrombinemia, methotrexate, monoamine oxidase inhibitors, naltrexone, nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, plicamycin, probenecid, sulfinpyrazone, urinary alkalizers, valproic acid, vancomycin, and zidovudineOther medical problems, especially coagulation or platelet function disorders, diarrhea caused by antibiotics or poisoning, asthma or other respiratory problems, and gastrointestinal problems such as ulceration or erosive gastritis (especially a bleeding ulcer) or other severe inflammatory bowel diseaseProper use of this medication» Taking with food or a full glass (240 mL) of water to minimize stomach irritation

» Not taking medication if it has a strong vinegar-like odor

» Importance of not taking more medication than the amount prescribed because of danger of overdose of aspirin or opioid analgesics and habit-forming potential of opioid analgesics

» Not increasing dose if medication seems less effective after a few weeks; checking with physician instead

» Proper dosing
Missed dose (if on scheduled dosing): Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storagePrecautions while using this medication
Regular visits to physician to check progress during long-term therapy

» Caution if other medications containing aspirin or other salicylates or opioid analgesics are used

» Avoiding use of alcohol or other central nervous system (CNS) depressants during therapy unless prescribed or otherwise approved by physician; also, alcohol consumption may increase risk of aspirin-induced stomach problems

Not taking acetaminophen or ibuprofen or other NSAIDs concurrently for more than a few days unless directed by physician or dentist

General Dosing Information
Medications containing aspirin should be administered with food or a full glass (240 mL) of water to lessen gastric irritation.

Opioid analgesics may depress respiration, especially in very young, elderly, very ill, or debilitated patients and those with respiratory problems. Lower doses may be required for these patients. However, elderly patients may also be more sensitive to the analgesic effects of these medications so that lower doses and/or a longer dosing interval may be sufficient to provide adequate analgesia.

Dosage of opioid analgesics should be individualized on the basis of the potency and duration of action of the specific agent used, the severity of pain, the condition of the patient, other medications given concurrently, and patient response.

Administration of aspirin concurrently with opioid analgesics provides additive analgesia and may permit lower doses of the opioid analgesic to be utilized.

Some clinicians recommend that patients in chronic severe pain receive opioid analgesics on a fixed dosage schedule in order that they remain free of pain rather than on an as needed basis after pain recurs.

Tolerance to many of the effects of opioid analgesics may develop with repeated administration. The first sign of tolerance is usually a decrease in the duration of effective analgesia. Patients who become tolerant to one of these agents may be partially cross-tolerant to the others.

If tolerance to the effects of the opioid analgesic should develop, an increase in dosage or decrease in dosing interval may be necessary. However, the analgesic efficacy of aspirin is subject to a ceiling effect; single doses larger than 1 gram may not provide additional therapeutic benefit (if the pain is not associated with severe inflammation), but chronic use of such doses will increase the risk of adverse effects, including gastrointestinal bleeding or ulceration. Therefore, administration of supplemental opioid analgesic, or administration of an opioid analgesic and aspirin separately, may be necessary to achieve adequate analgesia in opioid-tolerant patients.

Psychological and physical dependence may occur with chronic administration of opioid analgesics; an abstinence syndrome may occur when these medications are discontinued. Gradual withdrawal may minimize the development of withdrawal symptoms following prolonged use.

ASPIRIN AND CODEINE

Summary of Differences

Category:
Codeine is an opioid agonist analgesic.

Indications:
Indicated for relief of mild to severe pain, depending on the dose of codeine.

Elimination: Renal, 5–15% as unchanged codeine and 10% as unchanged or conjugated morphine.

Precautions:
Pregnancy—Codeine has been shown to cause delayed ossification in mice and increased resorptions in rats.

Breast-feeding—Codeine is distributed into breast milk.

Side/adverse effects:
Codeine is more likely than most other opioids to cause constipation, especially during chronic therapy.

Codeine has lower dependence liability and potential for abuse than most other opioid agonists with usual doses.

Withdrawal symptoms produced by codeine are less severe than those produced by stronger opioid agonist analgesics.

Oral Dosage FormsASPIRIN AND CODEINE PHOSPHATE TABLETS USPUsual adult dose
Oral, 1 or 2 tablets every four hours as needed.Usual pediatric dose
Dosage has not been established.Strength(s) usually available
U.S.—

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in the U.S.

Elimination: Renal, 5–15% as unchanged codeine and 10% as unchanged or conjugated morphine.

Precautions:
Pregnancy—Codeine has been shown to cause delayed ossification in mice and increased resorptions in rats.

Breast-feeding—Codeine is distributed into breast milk.

Drug interactions and/or related problems—Antacids present as buffering agents may decrease absorption of many orally administered medications; antacids generally should be taken 1 to 2 hours before or after other orally administered medications, although intervals of 3 to 8 hours between antacid ingestion and administration of specific agents (i.e., fluoroquinolone antibiotics, ketoconazole, and oral tetracyclines) have been recommended.

Side/adverse effects:
Codeine is more likely than most other opioids to cause constipation, especially during chronic therapy.

Codeine has lower dependence liability and potential for abuse than most other opioid agonists with usual doses.

Withdrawal symptoms produced by codeine are less severe than those produced by stronger opioid agonist analgesics.

Packaging and storage:
Store below 25 °C (77 °F), in a light-resistant container, unless otherwise specified by manufacturer. Store in a tight container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in the U.S.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in the U.S.

OXYCODONE AND ASPIRIN

Summary of Differences

Category:
Oxycodone is an opioid agonist analgesic.

Indications:
Indicated for relief of moderate to moderately severe pain.

Pharmacology/pharmacokinetics: For orally administered oxycodone:
Mechanism of action/effect: An opioid agonist analgesic; has agonist activity primarily at the mu receptor.

Precautions:
Breast-feeding—Not known whether oxycodone is distributed into breast milk.

Oral Dosage FormsOXYCODONE AND ASPIRIN TABLETS USPUsual adult dose
Analgesic
Oral, 1 or 2 half-strength tablets or 1 full-strength tablet, every four to six hours as needed. Dosage may be increased if necessary for severe pain.

Usual pediatric dose
Analgesic
Children up to 6 years of age—Use is not recommended.

Children 6 to 12 years of age—Oral, 1/4 half-strength tablet every six hours as needed.

Children 12 years of age and over—Oral, 1/2 half-strength tablet every six hours as needed.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in both the U.S. and Canada.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in the U.S.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in the U.S.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in Canada.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in Canada.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• Take with food or with a full glass of water.
• May be habit-forming.Note: Controlled substance in Canada.

Revised: 6/14/2000

References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.